Abstract
We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise-induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty-five young, untrained Caucasian adults performed 120 maximal eccentric knee-extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee-extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin-6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real-time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: ‘preferential’ (more ‘protective’ alleles), ‘moderate’, and ‘non-preferential’. The non-preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10−4) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN-AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene-cell-skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD.
Original language | English |
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Pages (from-to) | 2862-2876 |
Number of pages | 15 |
Journal | Journal of Cellular Physiology |
Volume | 237 |
Issue number | 7 |
Early online date | 21 Mar 2022 |
DOIs | |
Publication status | Published - Jul 2022 |
Bibliographical note
Funding Information:We are very grateful to Bethany Adams, Josephine Cabot, Victoria Edwards, Kelsie Johnson and Matthew Stanley for their help with data collection. This study was supported by a Leonardo da Vinci Grant (EAC/S07/2012) and partly by the EuroTech Postdoc Programme (Grant Agreement number 754462), co‐funded by the European Commission under its framework programme Horizon 2020 (both P.B.), and by a Wellcome Trust Biomedical Vacation Scholarship (207194/Z/17/Z; R.M.E.). Open access funding enabled and organized by Projekt DEAL.
Publisher Copyright:
© 2022 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.
Keywords
- eccentric exercise
- extracellular matrix (ECM)
- fibroblast
- myoblast
- single-nucleotide polymorphism (SNP)
- total genotype score (TGS)
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology